Inkcazo

I-Niraparib (MK-4827) inamandla kakhulu kunye ne-oral bioavailable PARP1 kunye ne-PARP2 inhibitor kunye ne-IC50 ye-3.8 kunye ne-2.1 nM, ngokulandelanayo.I-Niraparib ikhokelela ekuthinteleni ukulungiswa komonakalo we-DNA, isebenze i-apoptosis kwaye ibonise umsebenzi wokuchasana ne-tumor.

I-In vitro

I-Niraparib (MK-4827) inqanda umsebenzi we-PARP nge-EC50=4 nM kunye ne-EC90=45 nM kwi-cell assay yonke.I-MK-4827 inqanda ukwanda kweeseli zomhlaza kunye ne-BRCA-1 eguqukayo kunye ne-BRCA-2 kunye ne-CC50 kwi-10-100 nM uluhlu.I-MK-4827 ibonisa i-PARP 1 egqwesileyo kunye ne-2 inhibition nge-IC50=3.8 kunye ne-2.1 nM, ngokulandelelana, kunye ne-cell assay epheleleyo[1].Ukuqinisekisa ukuba i-Niraparib (MK-4827) inqanda i-PARP kule mizila yeeseli, iiseli ze-A549 kunye ne-H1299 ziphathwa nge-1.μI-M MK-4827 ngamaxesha ahlukeneyo kunye nokulinganisa umsebenzi we-PARP we-enzymatic usebenzisa i-chemiluminescent assay.Iziphumo zibonisa ukuba i-Niraparib (MK-4827) inqanda i-PARP ngaphakathi kwemizuzu ye-15 yonyango efikelela malunga ne-85% inhibition kwiiseli ze-A549 kwi-1 h kwaye malunga ne-55% inhibition kwi-1 h kwiiseli ze-H1299.

I-Niraparib (MK-4827) inyamezeleke kakuhle kwaye ibonisa ukusebenza njenge-arhente enye kwimodeli ye-xenograft ye-BRCA-1 yomhlaza osweleyo.I-Niraparib (MK-4827) inyamezeleke kakuhle kwi-vivo kwaye ibonisa ukusebenza njenge-arhente enye kwimodeli ye-xenograft ye-BRCA-1 yomhlaza osweleyo.I-Niraparib (MK-4827) ibonakaliswe nge-pharmacokinetics eyamkelekileyo kwiigundane kunye ne-plasma clearance ye-28 (mL / min) / kg, umthamo ophezulu kakhulu wokusabalalisa (Vd_ss= 6.9 L/kg), isiqingatha sobomi esibude (t_1/2=3.4 h), kunye ne-bioavailability egqwesileyo, F=65%^[1].I-Niraparib (MK-4827) iphucula impendulo ye-radiation ye-p53 ye-Calu-6 eguquguqukayo ye-tumor kuzo zombini iimeko, kunye nedosi enye yemihla ngemihla ye-50 mg / kg isebenza ngakumbi kune-25 mg / kg enikezelwa kabini imihla ngemihla.^].

Ugcino

Ubume beMichiza